BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action.
BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action.
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DOI：
10.1038/srep44861
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发表时间：
2017-03-20
影响因子：
4.6
通讯作者：
Fritsche E
中科院分区：
文献类型：
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作者：
Dach K;Bendt F;Huebenthal U;Giersiefer S;Lein PJ;Heuer H;Fritsche E
多溴联苯醚（PBDEs）是一种生物蓄积性阻燃剂，可对人类和啮齿动物造成发育神经毒性（DNT）。他们的DNT效应被怀疑涉及甲状腺激素（TH）信号中断。在这里，我们测试了BDE-99对神经祖细胞（NPC）分化为少突胶质细胞谱系（O 4+细胞）的干扰是否涉及对人类和小鼠（h，m）NPC中TH作用的破坏的假设。因此，我们量化了NPC向O 4+细胞的分化，并通过存在和不存在TH和/或BDE-99的情况下髓鞘相关基因（hMBP，mMog）的表达来测量其成熟。T3促进小鼠O 4+细胞分化，但不诱导hNPC，并诱导hMBP/mMog基因在两个物种中的表达。BDE-99减少了人类和小鼠O 4+细胞的生成，但没有迹象表明BDE-99会干扰O 4+细胞形成过程中的细胞TH信号。由于少突胶质细胞减少，BDE-99减少了hMBP的表达，但不影响小鼠O 4+细胞数量的浓度通过一种未知的机制抑制TH诱导的mMog转录。此外，抗坏血酸通过一种可能不依赖于活性氧的机制，仅拮抗人类而非小鼠O 4+细胞的BDE-99依赖性损失。这些数据表明，BDE-99对h/mNPC向少突胶质细胞谱系的发育具有物种特异性作用模式。
Polybrominated diphenyl ethers (PBDEs) are bioaccumulating flame retardants causing developmental neurotoxicity (DNT) in humans and rodents. Their DNT effects are suspected to involve thyroid hormone (TH) signaling disruption. Here, we tested the hypothesis whether disturbance of neural progenitor cell (NPC) differentiation into the oligodendrocyte lineage (O4+ cells) by BDE-99 involves disruption of TH action in human and mouse (h,m)NPCs. Therefore, we quantified differentiation of NPCs into O4+ cells and measured their maturation via expression of myelin-associated genes (hMBP, mMog) in presence and absence of TH and/or BDE-99. T3 promoted O4+ cell differentiation in mouse, but not hNPCs, and induced hMBP/mMog gene expression in both species. BDE-99 reduced generation of human and mouse O4+ cells, but there is no indication for BDE-99 interfering with cellular TH signaling during O4+ cell formation. BDE-99 reduced hMBP expression due to oligodendrocyte reduction, but concentrations that did not affect the number of mouse O4+ cells inhibited TH-induced mMog transcription by a yet unknown mechanism. In addition, ascorbic acid antagonized only the BDE-99-dependent loss of human, not mouse, O4+ cells by a mechanism probably independent of reactive oxygen species. These data point to species-specific modes of action of BDE-99 on h/mNPC development into the oligodendrocyte lineage.